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SarahC - Effective Altruism forum vieweren-usComment by SarahC on Cost-Effectiveness of Aging Research https://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research#comment-eZu8wnaHJaPbJRcCk
<p>It didn’t come from ei­ther, it came from me, as a bench­mark for what seems con­ser­va­tively pos­si­ble to achieve in the near-term, and for the size of im­pact nec­es­sary to be plau­si­bly cost-com­pet­i­tive with other causes like global poverty. (If the same amount of fund­ing yielded only one year’s de­lay in the DALY bur­den of age-re­lated dis­eases, I think that would make global poverty likely to be a “bet­ter buy.“)</p>SarahCeZu8wnaHJaPbJRcCkWed, 06 Feb 2019 18:30:23 +0000Comment by SarahC on Cost-Effectiveness of Aging Research https://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research#comment-EcvaTGPCpnsjQJm76
<p>I be­lieve there are larger effect sizes out there than met­formin; met­formin has a rel­a­tively small effect size on mice com­pared to other lifes­pan-mod­ify­ing in­ter­ven­tions, and the TAME trial chose met­formin (as Barzilai ad­mits) be­cause it’s ex­tremely safe and well-stud­ied, not be­cause it’s ex­pected to be the best.</p><p>I agree with you; I don’t think ag­ing re­search would be cost-effec­tive at a trillion dol­lars of to­tal fund­ing. I ex­pect that’s hugely more money than nec­es­sary.</p>SarahCEcvaTGPCpnsjQJm76Wed, 06 Feb 2019 18:26:41 +0000Comment by SarahC on Cost-Effectiveness of Aging Research https://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research#comment-neghBhLLJG86gsMyr
<p>Fixed, thanks.</p>SarahCneghBhLLJG86gsMyrWed, 06 Feb 2019 18:22:41 +0000Comment by SarahC on Cost-Effectiveness of Aging Research https://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research#comment-R7pKSehcxyHnBC6y4
<p>Yes, I’m aware, and thanks for ex­plic­itly flag­ging that.</p><p>DALY es­ti­mates are ob­vi­ously fraught, and I un­der­stand that they’re not ex­act for any par­tic­u­lar char­ity, but they seem seem rele­vant to back-of-the-en­velope cost-benefit think­ing about cause ar­eas.</p>SarahCR7pKSehcxyHnBC6y4Wed, 06 Feb 2019 18:21:52 +0000Comment by SarahC on Cost-Effectiveness of Aging Research https://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research#comment-7aBWCuWq9CYF95qcu
<p>This is a cor­rect point.</p><p>How­ever, I think it’s worth not­ing that the most strik­ing ad­vance in ag­ing re­search in re­cent years—the dis­cov­ery of senolyt­ics—came from biogeron­tol­o­gists, in­clud­ing those at the Buck In­sti­tute, which is ded­i­cated to ag­ing re­search. Nearly all stud­ies on lifes­pan are con­ducted by re­searchers who spe­cial­ize in ag­ing. In that sense, I think it’s fair to say that a good deal of ag­ing re­search comes from spe­cial­ized ag­ing re­searchers.</p><p>Cancer re­search, I think, should not be con­sid­ered ag­ing re­search, be­cause the vast ma­jor­ity of can­cer ther­a­pies are not also ag­ing-mod­ify­ing ther­a­pies. If ag­ing re­search pans out, of course, it will pro­duce ways to pre­vent or treat can­cer, but this will prob­a­bly not de­pend very closely on the vast cor­pus of gen­eral can­cer re­search.</p><p>Stem cell biol­ogy and ge­netic en­g­ineer­ing seem to fall into a differ­ent cat­e­gory, as im­por­tant <em>in­puts </em>to ag­ing re­search as well as to many other types of biomed­i­cal re­search. I don’t know if EAs have a gen­eral frame­work for eval­u­at­ing the cost-benefit trade­offs of more “up­stream” or “ba­sic” or “tool” re­search com­pared to “down­stream” or “trans­la­tional” or “ap­plied” re­search—ob­vi­ously the benefits of ba­sic re­search can be much larger than the benefits of trans­la­tional re­search, but the var­i­ance is also larger.</p><p>At any rate, my (non-quan­ti­ta­tive, ten­ta­tive) be­lief is that ag­ing-fo­cused <em>trans­la­tional </em>re­search is more un­der­funded than re­search into mul­ti­pur­pose biolog­i­cal tech­nolo­gies (like ge­netic en­g­ineer­ing or stem cell re­pro­gram­ming), but this may be chang­ing in the near fu­ture.</p>SarahC7aBWCuWq9CYF95qcuWed, 06 Feb 2019 18:19:43 +0000Comment by SarahC on Cost-Effectiveness of Aging Research https://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research#comment-5kRoCKMFxxA9DHrbk
<p>I might do more cost-effec­tive­ness es­ti­mates, but it’s not a top pri­or­ity—I’m cur­rently run­ning the <a href="https://thelri.org/">Longevity Re­search In­sti­tute</a>, a non­profit de­voted to ex­per­i­men­tally test­ing anti-ag­ing in­ter­ven­tions, and I have a lot of ob­ject-level work to do there. Definitely happy to con­sult, make in­tros, and share my own ex­ist­ing notes when­ever you have ques­tions.</p><p>Yes, my es­ti­mates are a large un­der­es­ti­mate of the po­ten­tial benefit of life-ex­tend­ing ther­a­pies if you as­sume that they ex­tend life at all, rather than just de­lay the on­set of dis­ease-re­lated dis­abil­ity. I wanted to in­di­cate that the im­pact is large even with rather pes­simistic as­sump­tions.</p>SarahC5kRoCKMFxxA9DHrbkWed, 06 Feb 2019 18:04:31 +0000Cost-Effectiveness of Aging Research by SarahChttps://ea.greaterwrong.com/posts/JsL2kPWJYRxn9rCWR/cost-effectiveness-of-aging-research
<p>(Cross­posted from Hour­glass Magaz­ine: <a href="https://hourglass.bio/blog/2018/9/27/cost-effectiveness-of-aging-research-why-solve-aging-part-3">https://​hour­glass.bio/​blog/​2018/​9/​27/​cost-effec­tive­ness-of-ag­ing-re­search-why-solve-ag­ing-part-3</a>)</p><p>Is ag­ing re­search a cost-effec­tive way of pre­vent­ing death and ill­ness? How does it com­pare to med­i­cal re­search more gen­er­ally, or to med­i­cal treat­ment, or to treat­ment of in­fec­tious dis­eases in poor coun­tries? </p><p>This post is go­ing to try to an­swer that ques­tion, in a quan­ti­ta­tive but very ap­prox­i­mate fash­ion.</p><p>If you want to play with the num­bers for your­self, you can check out the <a href="https://docs.google.com/spreadsheets/d/1tzSfcwoVyY5PsMz3PmyDj7LQWJ0gGgOdijoPuPJL8iw/edit#gid=1347797389">spread­sheet</a> or <a href="https://www.getguesstimate.com/models/11227">Guessti­mate model.</a></p><p>Dr. Owen Cot­ton-Bar­ratt of the Fu­ture of Hu­man­ity In­sti­tute and the <a href="http://globalprioritiesproject.org/">Global Pri­ori­ties Pro­ject</a> has writ­ten a <a href="http://globalprioritiesproject.org/category/prioritisation/uncertain-difficulty/">se­ries of es­says</a> on the cost-benefit pri­ori­ti­za­tion of “prob­lems of un­cer­tain difficulty”—that is, prob­lems where the amount of re­sources needed to solve them might be any­where be­tween many or­ders of mag­ni­tude, with roughly equal prob­a­bil­ity. Should you spend re­sources on re­search­ing these hard prob­lems to­day?</p><p>Well, it de­pends on how tractable the prob­lem is (how far along we are to­wards solv­ing it), how much benefit solv­ing it would offer us, and how ne­glected the prob­lem is (how much has already been in­vested into it.)</p><blockquote><em>Our model for the benefit of im­me­di­ate in­vest­ment said that the benefit was of size kB/​z. The three terms here line up pretty well with the com­po­nents of the three fac­tor model. The scale of the prob­lem is ex­pressed by B, the size of the benefit. The ne­glect­ed­ness gives us the term 1/​z, the re­cip­ro­cal of the amount of in­vest­ment so far. And the re­main­ing term, k, mea­sures the tractabil­ity of the prob­lem.</em><br></blockquote><p>Cot­ton-Bar­rett has a quan­ti­ta­tive ar­gu­ment for why the tractabil­ity of the prob­lem shouldn’t mat­ter much to our will­ing­ness to in­vest in it:</p><blockquote><em>Are there any les­sons to be drawn from this? One is that tractabil­ity may mat­ter less than the other two fac­tors. Un­der the box model dis­cussed, we have k*= p/​(ln(y/​z)), where y is some level of re­sources such that we be­lieve there is a prob­a­bil­ity p of suc­cess by the time y re­sources are in­vested. We might like to con­sider k= θk*, where θ is a fac­tor to ad­just for de­vi­a­tion from the box model. Then k it­self de­com­poses into three fac­tors: p, the like­li­hood of even­tual suc­cess; 1/​(ln(y/​z)), which tracks time we may have to wait un­til suc­cess; and θ, which ex­presses some­thing of whether we are cur­rently in a range where suc­cess is at all plau­si­ble.</em><br><em>If the prob­lem is some­thing that we be­lieve is likely to be out­right im­pos­si­ble, like con­struct­ing a per­pet­ual mo­tion ma­chine, then p will be very small and this will kill the tractabil­ity. If the prob­lem is nec­es­sar­ily hard and not solv­able soon, like send­ing peo­ple to other stars, then the box model will be badly wrong (or is best ap­plied with our cur­rent po­si­tion not even in the box), so θ can kill the tractabil­ity. But if it’s plau­si­ble that the prob­lem is sol­u­ble, and it might be easy — even if might also be ex­tremely hard — the re­main­ing com­po­nent of tractabil­ity is 1/​(ln(y/​z)). Be­cause of the log­a­r­ithm in this ex­pres­sion, it is hard for it to af­fect the fi­nal an­swer by more than an or­der of mag­ni­tude or so.</em></blockquote><p>As an ap­pli­ca­tion of this model, the Global Pri­ori­ties Pro­ject <u><a href="http://globalprioritiesproject.org/2015/02/estimating-the-cost-effectiveness-of-research-into-neglected-diseases/">es­ti­mate</a>s</u> that re­search into the ne­glected trop­i­cal dis­eases with the high­est global DALY bur­den (di­ar­rheal dis­eases) could be 6x more cost-effec­tive, in terms of DALYs per dol­lar, than the 80,000 Hours recom­mended top char­i­ties.</p><p>They also <a href="http://globalprioritiesproject.org/2015/02/research-note-how-valuable-is-medical-research/">es­ti­mate</a>, us­ing the same model, that med­i­cal re­search as a whole is be­ing un­der­in­vested in. They es­ti­mate the cost-effec­tive­ness of med­i­cal re­search as a whole at $8000/​QALY—worse than the best in­ter­ven­tions for global poverty (at $50/​QALY) but sig­nifi­cantly more cost-effec­tive than most health in­ter­ven­tions funded by the NHS (go­ing up to about $50,000/​QALY).</p><p>Now let’s use that same model to look at ag­ing re­search.</p><p><strong>Cost-Benefit Es­ti­mates of Aging Research</strong></p><p>The model Cot­ton-Bar­ratt recom­mends for first-pass Fermi es­ti­mates is</p><p>Ex­pected benefit = <em>p B/​(z </em>log<em>(y/​z))</em></p><p>Where <em>B</em> is the benefit in the case of suc­cess, z is the cur­rent spend­ing, and <em>p/​</em>log<em>(y/​z)</em> is the tractabil­ity, or the prob­a­bil­ity <em>p</em> of achiev­ing the goal once we’ve spent a given mul­ti­ple <em>y</em> of the cur­rent re­source spend <em>z</em>.</p><p>How does this ap­ply in the case of ag­ing?</p><p><strong>Benefit Considerations</strong></p><p>We imag­ine that a suc­cess­ful ag­ing in­ter­ven­tion will <em>shift the DALY bur­den of age-re­lated dis­ease later</em>, for con­crete­ness let’s say by ten years start­ing at age 50.</p><p> So a 60-year-old will have the dis­ease risk of a pre­sent-day 50-year-old, a 70-year-old will have the dis­ease risk of a 60-year-old, and so on. If we de­note by D_50 the ex­pected DALY bur­den of age-re­lated dis­ease on a 50- to 60-year-old and N_50 the num­ber of 50- to 60-year-olds in the world, the benefit of an ag­ing in­ter­ven­tion is:</p><p>B = N_60 (D_60-D_50) + N_70 (D_70-D_60) + N_80 (D_80-D_70) + N_90 (D_90- D_80).</p><p>The global DALY bur­dens for var­i­ous age-re­lated dis­eases at differ­ent ages, and the world pop­u­la­tions at those ages, are available from pub­lic statis­tics, so we can make an es­ti­mate of the benefit in terms of DALY gain per year from a suc­cess­ful anti-ag­ing in­ter­ven­tion. (This does not even ad­dress the is­sue that anti-ag­ing in­ter­ven­tions will also ex­tend life; so it’s a con­ser­va­tive es­ti­mate.)</p><p><strong>Ne­glect­ed­ness Considerations</strong></p><p>What is the cur­rent spend­ing level?</p><p>We can di­vide re­search on age-re­lated dis­ease into gen­eral ag­ing re­search and dis­ease-spe­cific re­search. If we con­sider only ag­ing re­search, then ag­ing re­search will ap­pear more ne­glected, and thus more cost-effec­tive; if we con­sider all age-re­lated dis­ease re­search (such as can­cer re­search, Alzheimer’s re­search, etc) ag­ing re­search will ap­pear less ne­glected and less cost-effec­tive. We’ll split the differ­ence by treat­ing the amount of ag­ing re­search as </p><p>A + theta O</p><p>Where A is ag­ing-spe­cific re­search, O is re­search into other age-re­lated dis­ease, and theta is a weight be­tween 0 and 1 to rep­re­sent how much we think dis­ease-spe­cific re­search “counts.”<br></p><p><strong>Sources</strong></p><p>For the DALY bur­den of the dis­eases of ag­ing we use the <a href="http://ghdx.healthdata.org/gbd-results-tool">Global Bur­den of Disease 2016</a> statis­tics.</p><p>For es­ti­mates of the amount of ag­ing spend­ing we use the Na­tional In­sti­tute of Aging’s <a href="https://www.nia.nih.gov/about/budget/fiscal-year-2018-budget/fy-2018-justification-budget-request">2016 bud­get</a>, the bud­gets of var­i­ous EU re­search or­ga­ni­za­tions[1], the R&amp;D bud­get of <a href="https://www.nasdaq.com/press-release/unity-biotechnology-inc-reports-first-quarter-2018-financial-results-20180607-01117">Unity Biotech­nol­ogy</a>, and spend­ing on “senes­cence” or “re­gen­er­a­tive medicine” from the <a href="https://pharmacognitive.com/">Pharma Cog­ni­tive</a> database. </p><p>For es­ti­mates of the amount of age-re­lated dis­ease spend­ing we use the Na­tional In­sti­tute of Health’s <a href="https://report.nih.gov/categorical_spending.aspx">2017 bud­get</a> and the <a href="https://www.ifpma.org/wp-content/uploads/2017/02/IFPMA-Facts-And-Figures-2017.pdf">IFPMA’s es­ti­mates</a> of 2017 pharma R&amp;D spend­ing.</p><p>For ex­perts’ es­ti­mates of the tractabil­ity of ag­ing spend­ing, we use Aubrey De Grey’s pre­dic­tions[2] as an op­ti­mistic es­ti­mate, and the UK Longevity Panel’s pre­dic­tions[3] as a pes­simistic es­ti­mate.</p><p>We have high un­cer­tainty around all of these num­bers, but es­pe­cially of the amount of ag­ing spend­ing, since there’s no good way to es­ti­mate, to my knowl­edge, how much is be­ing spent in phar­ma­ceu­ti­cal R&amp;D on ag­ing drugs, and no good data on the amount of ag­ing re­search dol­lars spent by pri­vate or­ga­ni­za­tions, some of which, like Cal­ico, may be quite well-funded. What counts as “ag­ing re­search” is also a some­what sub­jec­tive judg­ment; some ag­ing re­search may not la­bel it­self as such, and some re­search la­beled “ag­ing” may ac­tu­ally be dis­ease-spe­cific re­search not rele­vant to the un­der­ly­ing biol­ogy of ag­ing.<br></p><p><strong>Results</strong></p><p>Our es­ti­mates of to­tal cur­rent ag­ing re­search spend­ing are <strong>$1.8 billion-4.5 billion,</strong> and we es­ti­mate a log-lin­ear dis­tri­bu­tion (the modal amount of spend­ing is likely on the low end, close to the NIH’s ag­ing bud­get, but there may be a long tail al­low­ing for much higher spend­ing, es­pe­cially if pri­vate drug com­pa­nies have more ag­ing-re­lated R&amp;D than pub­lic databases es­ti­mate.)</p><p>Our rough es­ti­mate of to­tal age-re­lated dis­ease spend­ing is <strong>$104 billion</strong>, and we es­ti­mate a nor­mal dis­tri­bu­tion.</p><p>Our es­ti­mate of tractabil­ity is uniformly dis­tributed be­tween 0.1 and 1, with mean <strong>0.56</strong>; this fol­lows the “un­cer­tain chance of suc­cess” model in Cot­ton-Bar­ratt’s calcu­la­tions.</p><p>Our es­ti­mate of to­tal benefit from de­lay­ing ag­ing by 10 years is <strong>176,800,000</strong> DALYs saved yearly wor­ld­wide, plus or minus 30M DALYs, and we as­sume a nor­mal dis­tri­bu­tion. </p><p>For theta=0 (only ag­ing-spe­cific re­search counts) the cost-effec­tive­ness is about <strong>$42/​DALY.</strong></p><p>For theta=1 (all age-re­lated dis­ease R&amp;D counts), the cost-effec­tive­ness is about <strong>$1050/​DALY, </strong>more effec­tive than GPP’s es­ti­mates of med­i­cal re­search as a whole.<br></p><p><strong>Bot­tom Lines</strong></p><p>With a very rough and pre­limi­nary anal­y­sis, it looks like ag­ing re­search could be com­pa­rable or su­pe­rior in cost-effec­tive­ness to the most cost-effec­tive global health in­ter­ven­tions.</p><p>GiveWell <a href="https://docs.google.com/spreadsheets/d/13b_qt-G_TQtoYNznNak3_5dzvzgCSUPJnk3l5dMisJo/edit#gid=1034883018">es­ti­mates</a> a cost of $1965 for a gain of <a href="https://blog.givewell.org/2016/12/12/amf-population-ethics/">~8</a> DALY-equiv­a­lents, or $437.50 per DALY, from giv­ing malaria-pre­vent­ing mosquito nets to chil­dren in de­vel­op­ing coun­tries. Th­ese es­ti­mates have changed quite a bit over time—some <a href="https://www.givingwhatwecan.org/report/against-malaria-foundation/">older num­bers</a> from the re­search liter­a­ture es­ti­mate $14-110 per DALY from mosquito nets. </p><p>This means the es­ti­mated cost-effec­tive­ness of ag­ing re­search (even with a con­ser­va­tive value of theta) is solidly com­pet­i­tive with even the best cost-effec­tive­ness num­bers for de­vel­op­ing-world char­i­ties.</p><p>Of course, ag­ing re­search is much more spec­u­la­tive than di­rectly treat­ing or pre­vent­ing dis­ease by known meth­ods. If you want to buy a sure thing, re­search of any kind is not a great choice. Ad­di­tion­ally, these back-of-the-en­velope cost-effec­tive­ness es­ti­mates are much more spec­u­la­tive them­selves than the abun­dant em­piri­cal re­search on trop­i­cal dis­ease pre­ven­tion.</p><p>Another con­sid­er­a­tion is that ag­ing is a much <em>big­ger </em>prob­lem, in to­tal, than any spe­cific dis­ease. The to­tal DALY bur­den of the dis­eases of ag­ing is about 700 mil­lion DALYs, whereas the to­tal DALY bur­den of malaria is about 50 mil­lion, or more than 10x smaller.</p><p>If you like high-risk, high-re­turn, cost-effec­tive life­sav­ing pro­jects, then med­i­cal re­search in gen­eral may be a good buy, and ag­ing re­search es­pe­cially so, be­cause the level of ex­ist­ing fund­ing is so low, and the size of the im­pact of suc­cess is so high.</p><p><strong>References</strong></p><p>[1]Ge­hem, Maarten, and Paula Sánchez Díaz. Shades of gray­ing: re­search tack­ling the grand challenge of ag­ing for Europe. The Hague Cen­tre for Strate­gic Stud­ies, 2013.</p><p>[2]De Grey, Aubrey DNJ. “Life span ex­ten­sion re­search and pub­lic de­bate: so­cietal con­sid­er­a­tions.” <em>Stud­ies in Ethics, Law, and Tech­nol­ogy</em> 1.1 (2007).</p><p>[3]<a href="http://www.longevitypanel.co.uk/_files/What-is-ageing-can-we-delay-it.pdf" class="bare-url">http://​​www.longevi­ty­panel.co.uk/​​_files/​​What-is-age­ing-can-we-de­lay-it.pdf</a></p>SarahCJsL2kPWJYRxn9rCWRThu, 31 Jan 2019 20:47:49 +0000